Phase 1, 2-Cohort, Open-label, Fixed-sequence, Drug-drug Interaction Study to Evaluate the Effect of Repotrectinib on the Pharmacokinetics of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Cohort 1: Renal Clearance (CLR) of Metformin in Urine
研究概览
简要总结
The purpose of the study if to evaluate the effect of Repotrectinib on the drug levels of transporter and CYP P450 probe substrates in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must have a body mass index (BMI) of 18.0 to 32.0 kg/m2 and should be between the ages of 18-60 years inclusive.
- •Healthy female (as assigned at birth) participants who are individuals not of childbearing potential (INOCBP) and healthy males with no clinically significant deviation from normal for the following: medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory assessment results as determined by the investigator.
排除标准
- •Participants must not have a significant history of clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, psychiatric, neoplastic, or genitourinary abnormalities/diseases as determined by the investigator or designee.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Cohort 2
干预措施: Omeprazole (Drug)
Cohort 1
干预措施: Repotrectinib (Drug)
Cohort 1
干预措施: Metformin (Drug)
Cohort 1
干预措施: Digoxin (Drug)
Cohort 1
干预措施: Rosuvastatin (Drug)
Cohort 2
干预措施: Repotrectinib (Drug)
Cohort 2
干预措施: Bupropion (Drug)
Cohort 2
干预措施: Flurbiprofen (Drug)
结局指标
主要结局
Cohort 1: Renal Clearance (CLR) of Metformin in Urine
时间窗: Up to approximately Day 16 post dose
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to 48 Hours Post Dose (AUC (0-48)) of Metformin With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Cohort 1: AUC (0-48) of Metformin Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of AUC (0-T) of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin.
Cohort 1: AUC (0-T) of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin.
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin.
Cohort 1: AUC(INF) of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin.
Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin
Cohort 1: Cmax of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains metformin, digoxin, and rosuvastatin
Cohort 2: AUC (0-T) of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
Cohort 2: AUC (0-T) of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
Cohort 2: AUC (INF) of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
Cohort 2: AUC (INF) of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
Cohort 2: Cmax of Probe Substrate With Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
Cohort 2: Cmax of Probe Substrate Without Repotrectinib
时间窗: Up to approximately Day 17 post dose
Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)
次要结局
- Number of Participants with Adverse Events (AEs)(Up to approximately Day 45 post dose)
- Number of Participants with Serious Adverse Events (SAEs)(Up to approximately Day 45 post dose)
- Number of Participants With Clinically Significant Physical Examination Findings(Up to approximately Day 17 post dose)
- Number of Participants With Clinically Significant Vital Sign Measurements(Up to approximately Day 17 post dose)
- Number of Participants With Clinically Significant 12-lead Electrocardiogram (12-lead ECG) Findings(Up to approximately Day 17 post dose)
- Number of Participants With Clinically Significant Safety Laboratory Test Results(Up to approximately Day 17 post dose)